Acne vulgaris is a skin disease of youths involving comedos, papulae, pustules, etc. appearing on the face, the center of the chest, the upper part of the back, etc. Main causes of acne vulgaris include (1) excessive secretion of sebum, (2) stricture of hair-follicles, and (3) proliferation of Propionibacterium acnes, one of Gram positive anaerobic bacteria, in the pilosebaceous gland.
Conventional treatments of acne vulgaris are focused on removal of the above-described three main causes. For example, female hormones are applied to suppression of sebum secretion; keratolytic substances, e.g., salicylic acid, resorcin, etc. are applied to elimination of stricture of hair-follicles; and bactericidal disinfectants, e.g., Chlorhexidine Gluconate, is applied to inhibition of proliferation of the bacterium.
Caryophyllene, cedrene, longifolene, and thujopsene which are used as active ingredients in the present invention are known substances belonging to sesquiterpene hydrocarbons which can easily be isolated from trees by extraction and have hitherto been utilized as raw materials of compounded perfumes, such as soap perfumes, or raw materials in perfume production. It is known that these substances generally have weak antibacterial activity as one of physiological activities, and there is found no literature referring to utility as antibacterials. For instance, B. B. Dey, et al. report in Indian Perfumer, 28(2), 82-87 (1984) that antimicrobial tests on several fungi, Escherichia coli, etc. revealed strong antimicrobial activity of eugenol known to be present in clove oil similarly to caryophyllene but no activity of caryophyllene. Further, Itoh Masaaki, et al. report in J. Antibact. Antifung. Agents, 8(1), 3-6 (1980) that any substantial antimicrobial activity on various molds, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa was not exhibited by thujopsene per se extracted from hiba oil but by some of derivatives synthesized therefrom.
With reference to treatment of acne vulgaris by a plant component as an active ingredient, JP-A-63-150208 (the term "JP-A" as used herein means an "unexamined published Japanese patent application" discloses that an extract of trees of the hinoki family, e.g., Thujopsis dolabrata Sieb, et Zucc., exhibits antimicrobial activity on Propionibacterium acnes and can be incorporated into agents for topical application to the skin. However, the publication does not refer to isolation of the active ingredient. Further, JP-A-1-151522 corresponding to Canadian Patent 1,273,576 and EP-A-0 308 210 proposes to treat acne vulgaris with eucalyptol, menthol or thymol included in monoterpene alcohols in combination with other active ingredients. However, there is no literature on cases of using a sesquiterpene hydrocarbon for treatment of acne vulgaris or on inhibitory or bactericidal activity of a sesquiterpene hydrocarbon on Propionibacterium acnes.
Bactericidals conventionally used for inhibition of proliferation of bacteria as an approach to treatment of acne vulgaris, such as Chlorhexidine Gluconate, have side effects of causing erythema or exfoliation, causing extreme skin roughening and skin irritation. It has therefore been difficult to obtain the full effect of such bactericidals due to their limited allowable dose.